Immune incompetence and autoimmunity are important, not mutually exclusive, expressions of disordered regulation of the immune response. In the former, selective or general deficiencies of T helper cell activity rob the host of the capacity to produce immune effectors, placing the host at risk to infection with opportunistic pathogens. In the latter, excessive activity of helper cells (or selective deficiencies of suppressor T cells) permit the local elaboration of lymphokines which activate precursor cells directed at tissue specific (self) molecules. We propose that the principle factors responsible for immune-based diseases that occur within specific tissues/organs reside within these tissues. Our plan is to study tissue-localized cells and molecules of the immune system in order to gain insight into the pathogenic processes and thereby be in a position to suggest advances in prevention, diagnosis, and therapy. Eight recently recruited immunobiologists on the faculty at U. of Miami School of Medicine, in collaboration with seven clinical immunologists/investigators have developed an interdepartmental research program to study disorders of immune regulation. Four human diseases have been singled out: Hyperthyroidism (Graves' Disease); Insulin Dependent Diabetes Mellitus (Juvenile type); Pneumocystis carinii pulmonary infection in Acquired Immune Deficiency Syndrome; and Cytomegalovirus Retinitis in Immunocompromised patients. Five research projects, and supporting administration and core laboratory, are proposed and share in common the following: (1) Each project utilizes patient material (tissues/fluids) which will be analyzed for content of immune effector cells and molecules, in part through the technology of cloning; (2) each study utilizes a murine model which is reasonably representative of the human disorder, for comparison's sake; and (3) a battery of techniques applicable to human as well as mouse material will be developed so that individual investigator strengths and technical capabilities can be made generally available for the enrichment and advancement of each project.